The present proposal, devoted to the regulation of the ventilation and of the pulmonary circulation, is concerned with the normal interplay between the circulatory and respiratory systems. This proposal is to continue a line of work that was initiated more than fifteen years ago. It is based on the premise that the heart and lungs are part of a coordinated system to satisfy tissue needs for oxygen at rest and during exercise. Over the years, each element in the system has been examined separately in order to determine its characteristics and its physiologic responses, and regulatory mechanisms have been explored to uncover how coordination is effected. In the present proposal, this approach is typified by our studies on the control of breathing: emphasis has now shifted from the original concern with the effects of chemical stimuli on the ventilation to the current interest in the neuophysiological contributions to the ventilatory drive. Also, in line with our comparative biological approach, research continues on the lungfish, the first animal to move from life in water to residence on land. A similar evolution in our research is exemplified by our studies of the pulmonary circulation: from the original concerns wit pulmonary blood pressures, flow, and volumes, attention now is directed at water and macromolecular exchanges in the pulmonary microcirculation, with particular reference to structural-functional relationships. Finally, as part of our approach to the coordinated operation of the lungs, heart, and pulmonary circulation, we have understaken to explore how the right ventricle adjusts to different types of pressure and flow loads, in health and in disease.